Wk 8: Impact of Circadian Dysfuntion

  1. Two process model
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  2. Interaction between circadian and homeostatic influences
    • Paradoxical” phase relationship between circadian drive for sleep and habitual sleep time in normal conditions: Peak in circadian drive for wakefulness in the evening, Peak in circadian drive for sleep in the early morning
    • Circadian drive for wakefulness opposes the homeostatic drive for sleep in the evening (just prior to normal bedtime)- helps maintain wakefulness
    • Circadian drive for sleep increases as the homeostatic drive for sleep declines over the course of the sleep episode – helps maintain consolidated sleep
  3. Measuring the influence of circadian time on sleep:
    Forced Desynchrony Protocol
    • Force the sleep/wake into desynchrony of circadian time
    • sleep-wake cycle length far from intrinsic period
    • reduced light-dark cycle strength
    • light and darkness distributed across circadian phases
    • core body temperature, melatonin and performance generally measured
  4. Sleep quality depends on circadian phase
    • Good sleep when it aligns with min core body temp
    • Short sleep if sleep at min core or not at min core at all
    • Sleep too long if you fall asleep at max temp
  5. Influence of circadian time increases with increased sleep restriction
    • As time went on, and more chronic sleep loss, the greater the influence of circadian time
    • eg. slower reaction time
    • Performance across a day can be determined by the circadian time of wake
  6. Women have an advanced phase- implications
    • The advanced phase in women may affect the quality of sleep
    • Men sleeping at an ideal circadian time for the maintenance of an 8 hour consolidated sleep bout.
    • Women may be more vulnerable to sleep maintenance insomnia and early-morning awakening
  7. Circadian rhythms and metabolic health
    • Sleep insufficiency: too little sleep
    • Circadian misalignment: eating out of phase with clock
    • Circadian disruptions: disturbing the clock with light
  8. Association between BMI & Sleep Duration
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    • Greater effect on women
  9. Sleep restriction impacts glucose tolerance
    • Under sleep debt: clear out glucose slower
    • Insulin (needed to clear out glucose) is also less active
  10. Effect of sleep duration on leptin and ghrelin levels
    • Leptin and ghrelin: balances hunger and satiety levels
    • Leptin: satiety
    • Ghrelin: hunger
    • Less sleep: more ghrelin, less leptin
  11. Sleep Duration is related to Leptin
    The more sleep you get, the more leptin and less ghrelin
  12. Circadian misalignment suppresses leptin levels
    When someone is misaligned (sleeping at wrong time), lower leptin (satiety) and thus eat more
  13. Circadian misalignment reduces glucose tolerance and insulin sensitivity
    Response is like diabetic
  14. Circadian disruption with light
    • Disruption of circadian rhythms in rodents with light results in:
    • Weight gain
    • Increased plasma insulin
    • Reduced insulin sensitivity
    • Chronically sleep depriving rats without stress or circadian disruption results in:
    • No metabolic effects
  15. ‘Social jet lag’ and obesity
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    • The people with the most circadian misalignment from weekdays to weekends, have the worst weight issues (for those already overweight)
    • Those with lower BMI have smaller association
  16. Our cardiovascular system is remarkably different in the Day vs. the Night
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  17. From a CV perspective
    • - Rhythm disturbances/shift work are associated with an increased risk of heart disease,
    • - adverse CV events
    • - worse outcomes
  18. Circadian rhythm disturbance increase cardiovascular disease
    • Shift workers are at increased risk of CVD and this may be due to the impact of light at night on rhythm disturbance.
    • Animal models show that disturbed rhythms lead to profound cardiovascular disease.
    • Disturbing circadian rhythms with light leads to CVD
  19. Light decreases melatonin, increasing cancer risk
    • In 2007, the International Agency for Research on Cancer concluded that shift work is “probably carcinogenic to humans,” based in large part on the growing association between night-shift work and increased incidence of breast cancer.
    • More melatonin, less tumor proliferation.
    • Total visual blindness is protective against breast cancer
  20. Circadian rhythms and depression
    • Focus on Phase and Amplitude
    • Moving off an ideal circadian phase relates to Seasonal Affective Disorder (SAD) severity
    • SAD: they tend to be more delayed
    • Adjusting phase toward an idea time improves mood in SAD
  21. Major depressive disorder
    • Delayed melatonin secretion correlates with symptom severity
    • Morning bright light therapy
    • Light therapy works for nonseasonal depression in high quality studies and where light is used in the morning (advances clock)
  22. Why does a phase delay matter?
    The circadian time of wake impacts performance across the day
  23. Depression and amplitude
    • Amplitude reduction in depression a common finding
    • Amplitude reduction is associated with symptom severity
    • Recovery associated with normalizing amplitude
  24. Light sensitivity
    • Light sensitivity is increased in bipolar disorder
    • Low light sensitivity in current depression: potential biomarker of depression
    • A state marker- light sensitivity changes based on mood
  25. Circadian Phase Advance in Current, Unmedicated Depression
    • Perfect phase angle
    • Advance phase for those with depression maybe because of decreased sensitivity to light (responding less).
    • Low light sensitivity leads to a decreased response to light at night, causing overall advances in timing and inappropriate circadian time of sleep
  26. The SSRI citalopram: effect on circadian light sensitivity
    • The SSRI citalopram greatly increases light sensitivity
    • Less efficacy for evening type people, irregular bed times and exposure of light at night because of increased sensitivity
Card Set
Wk 8: Impact of Circadian Dysfuntion
Wk 8: Impact of Circadian Dysfuntion